641 research outputs found

    Passive vibration absorber with dry friction

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    Post臋py w badaniach nad mechanizmem dzia艂ania IVIg

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    Cz膮steczka IgG stanowi g艂贸wny sk艂adnik do偶ylnych preparat贸w immunoglobulin (IVIg, intravenous immune globulin). Komercyjne preparaty IVIg pochodz膮 od grupy dawc贸w, w wyniku czego zawieraj膮 r贸wnie偶 niewielkie ilo艣ci przeciwcia艂 IgA, IgM, a tak偶e cytokiny Th2 oraz antagonist贸w cytokin. Substancje te r贸wnie偶 wp艂ywaj膮 na efekt terapeutyczny. Podstawowe znaczenie dla dzia艂ania IVIg maj膮: kom贸rki T, cytokiny, zjawisko przechodzenia kom贸rek odporno艣ciowych przez b艂ony biologiczne, kom贸rki B, dope艂niacz oraz receptory Fc. Stwierdzono, 偶e IVIg inaktywuj膮 autoreaktywne kom贸rki T poprzez wsp贸艂zawodniczenie i przerywanie ich interakcji z kom贸rkami prezentuj膮cymi antygen. Wydaje si臋, 偶e IVIg przywracaj膮 r贸wnie偶 r贸wnowag臋 w dzia艂aniu cytokin - w badaniach wykazano, 偶e IVIg zawieraj膮 przeciwcia艂a i antagonist贸w dla cytokin prozapalnych. Dodatkowo, uwa偶a si臋, 偶e IVIg ingeruje i zapobiega przechodzeniu autoodporno艣ciowych –kom贸rek T przez barier臋 krew-nerw. Badano efekty dzia艂ania egzogennych przeciwcia艂 na kom贸rki B. Uwa偶a si臋, 偶e IVIg zmniejszaj膮 produkcj臋 przeciwcia艂 przez kom贸rki B, zak艂贸caj膮 proliferacj臋 kom贸rek B poprzez blokad臋 receptor贸w powierzchniowych kom贸rki i zapobiegaj膮 aktywacji pewnych podtyp贸w kom贸rek B. Ponadto IVIg mog膮 wp艂ywa膰 na odporno艣膰 wrodzon膮 poprzez mechanizm blokowania w kaskadzie aktywacji dope艂niacza oraz blokowanie aktywno艣ci, w kt贸rej po艣redniczy receptor Fc, co powoduje zmniejszenie aktywno艣ci makrofag贸w. Podsumowuj膮c, IVIg charakteryzuj膮 si臋 licznymi mechanizmami dzia艂ania, kt贸rych efekty kumuluj膮 si臋 w celu ograniczenia odpowiedzi immunologicznej. Mo偶e to by膰 istotne w leczeniu zaburze艅 nerwowo-mi臋艣niowych oraz neuropatii immunologicznych. Polski Przegl膮d Neurologiczny 2009; 5 (4): 208-21

    The adenosinergic signaling in the pathogenesis and treatment of multiple sclerosis

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    Multiple sclerosis (MS) is a highly disabling, progressive neurodegenerative disease with no curative treatment available. Although significant progress has been made in understanding how MS develops, there remain aspects of disease pathogenesis that are yet to be fully elucidated. In this regard, studies have shown that dysfunctional adenosinergic signaling plays a pivotal role, as patients with MS have altered levels adenosine (ADO), adenosine receptors and proteins involved in the generation and termination of ADO signaling, such as CD39 and adenosine deaminase (ADA). We have therefore performed a literature review regarding the involvement of the adenosinergic system in the development of MS and propose mechanisms by which the modulation of this system can support drug development and repurposing

    Multiple sclerosis: time for early treatment with high-efficacy drugs

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    This review addresses current changes in the approach to treating patients with multiple sclerosis (MS). The widely practiced approach of utilizing agents with lower treatment efficacy (LETA) at onset with subsequent escalation has been challenged by new data suggesting that MS patients derive greater benefit when therapy is initiated with high-efficacy treatment agents (HETA). Several recent studies compared treatment efficacy and safety of early administration of HETA versus LETA. The results of randomized, double blind, phase III studies with LETA as a control arm and population-based larger and longer studies using propensity scoring, marginal structural modeling and weighted cumulative exposure analysis support the benefit of early treatment with HETA. Patients initiating their treatment with HETA, regardless of prognostic factors and MRI burden at baseline, showed significantly lower annualized relapse rate (ARR) and reduced disability progression in follow-up periods of up to 10鈥15 years. Moreover, the safety profile of recently approved HETA ameliorates concerns about off-target effects associated with a number of earlier high-efficacy drugs. Patient perception has also changed with an increasing preference for medication profiles that both improve symptoms and prevent disease progression. Accumulating data from randomized studies and the results of large population-based studies demonstrating short-term and longer-term patient benefits support the view that HETA should be more widely used. The adoption of early treatment with HETA capitalizes on a window of opportunity for anti-inflammatory drugs to maximally impact disease pathology and heralds a sea change in clinical practice toward pro-active management and away from a philosophy routed in generating clinical benefit as a consequence of treatment failure

    Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy:Results of the ProCID Study

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    Background and Aims:聽The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga庐) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings.聽Methods:聽Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks.聽Results:All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64鈥90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication.聽Interpretation:Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP.聽Clinical trial numbers:聽EudraCT 2015-005443-14, NCT02638207.</p
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